1. Technical Field
The invention relates to methods and materials involved in the treatment and prevention of non-invasive fungus-induced inflammation of mucosal tissue as well as asthma symptoms.
2. Background Information
Mucositis, the inflammation of mucosal tissue, is a serious medical problem that affects millions of people worldwide. For example, conservative estimates indicate that between 20 to 40 million Americans suffer from chronic rhinosinusitis, an inflammation of the nasal cavity and/or paranasal sinuses.
For the most part, the cause of chronic rhinosinusitis is unknown. In a small percentage of patients, however, non-invasive fungal organisms living within mucus seem to be involved. Patients having this condition, now known as allergic fungal sinusitis (AFS), were first described in the early 1980's (Miller J W et al., Prod. Scot. Thor. Soc. 36:710 (1981) and Katzenstein A L A et al., J. Allergy Clin. Immunol. 72:89-93 (1983)). Specifically, about three to eight percent of chronic rhinosinusitis cases requiring surgery because of nasal obstruction caused by polyp formation have been classified as AFS. Briefly, AFS is diagnosed by the presence of inspissated mucus in the nasal-paranasal cavities. Typically, this mucus contains clumps or sheets of necrotic eosinophils, Charcot-Leyden crystals, and non-invasive fungal hyphae. In addition, patients with AFS typically have a history of nasal-paranasal polyposis and may have undergone multiple surgeries. Inflammation can affect all nasal-paranasal cavities, but also can be asymmetric involving only one side. Computed topography (CT) scans of patients with AFS have a characteristic appearance and often reveal bone erosion in adjacent structures. Indeed, destruction of bones adjacent to the sinuses and nasal areas ranging from 19 percent to 80 percent has been reported.
Although fungal organisms seem to be the causative agent of AFS, successful treatment remains lacking. Currently, AFS patients as well as most chronic rhinosinusitis patients receive surgical treatment with or without steroid therapy. Surgery helps clear the nasal-paranasal cavities when obstructed by polyps and steroid therapy helps control inflammatory responses that seem to be causing tissue and bone destruction. Unfortunately, patients treated with surgery alone almost always experience recurrent rhinosinusitis symptoms and additional polyp growth. In addition, prolonged use of steroids is associated with significant side effects and steroid therapy removal also leads to recurrent episodes of rhinosinusitis. For these reasons, people suffering from chronic rhinosinusitis conditions typically experience repeated cycles of intense inflammation, surgery, and steroid therapy followed by recurrent intense inflammation. Thus, neither surgery nor steroid therapy is particularly effective or desirable as a long-term treatment for chronic rhinosinusitis conditions.